The project will determine the role of heart cAMP-dependent protein kinase in the regulation of cardiac contractility and metabolism. The effects of a number of cardioactive hormones and drugs, both those which raise cAMP and those which have no effect or lower cAMP levels, on protein kinase activity will be measured. Comparisons will be made between protein kinase activity and various metabolic and functional parameters thought to be regulated by cAMP. The in vivo phosphorylation of specific heart proteins thought to be cAMP-dependent protein kinase substrate will be studied. The possibility of a cAMP-independent mechanism for the activation of the heart cAMP-dependent protein kinase will be investigated. The effects of ischemia and hypoxia on heart protein kinase will be studied.